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Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions.

Lavstsen T, Salanti A, Jensen AT, Arnot DE, Theander TG - Malar. J. (2003)

Bottom Line: Two sequences belonging to the var1 and var2 subfamilies formed independent groups.A rif subgroup transcribed towards the centromere was found neighbouring var genes of group A such that the rif and var 5' regions merged.This organization appeared to be unique for the group A var genes The grouping of var genes implies that var gene recombination preferentially occurs within var gene groups and it is speculated that the groups reflect a functional diversification evolved to cope with the varying conditions of transmission and host immune response met by the parasite.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Medical Parasitology at Institute for Medical Microbiology and Immunology, University of Copenhagen, Denmark. thomaslavstsen@vip.cybercity.dk

ABSTRACT

Background: The variant surface antigen family Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) is an important target for protective immunity and is implicated in the pathology of malaria through its ability to adhere to host endothelial receptors. The sequence diversity and organization of the 3D7 PfEMP1 repertoire was investigated on the basis of the complete genome sequence.

Methods: Using two tree-building methods we analysed the coding and non-coding sequences of 3D7 var and rif genes as well as var genes of other parasite strains.

Results: var genes can be sub-grouped into three major groups (group A, B and C) and two intermediate groups B/A and B/C representing transitions between the three major groups. The best defined var group, group A, comprises telomeric genes transcribed towards the telomere encoding PfEMP1s with complex domain structures different from the 4-domain type dominant of groups B and C. Two sequences belonging to the var1 and var2 subfamilies formed independent groups. A rif subgroup transcribed towards the centromere was found neighbouring var genes of group A such that the rif and var 5' regions merged. This organization appeared to be unique for the group A var genes

Conclusion: The grouping of var genes implies that var gene recombination preferentially occurs within var gene groups and it is speculated that the groups reflect a functional diversification evolved to cope with the varying conditions of transmission and host immune response met by the parasite.

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Related in: MedlinePlus

A) Schematic presentation of all 3D7 var gene sequence analyses. Gene names, chromosomal location, transcriptional direction and domain structure are shown along with the cluster to which each gene was assigned by the sequences analyses. Sequences that could not be assigned to any cluster were named X. Three major var gene groups (group A-C), two intermediate groups group B/A and group B/C and two unique genes representing var1 and var2 var gene families were defined (framed). B) Sequence analyses of var genes from other P. falciparum strains than 3D7. Protein accession numbers, originating strain, domain structure and the closest related 3D7 var 5' sequence are shown along with sequence group allocations as defined in 3D7. *) The genes were assigned to group A, as their DBL1α sequences clustered together with other group A sequences in analysis of DBLα sequences. **) Pseudogene, belongs to the var1 family ^) Upstream sequences with atypically low similarity to upsB or upsC sequences.
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Figure 7: A) Schematic presentation of all 3D7 var gene sequence analyses. Gene names, chromosomal location, transcriptional direction and domain structure are shown along with the cluster to which each gene was assigned by the sequences analyses. Sequences that could not be assigned to any cluster were named X. Three major var gene groups (group A-C), two intermediate groups group B/A and group B/C and two unique genes representing var1 and var2 var gene families were defined (framed). B) Sequence analyses of var genes from other P. falciparum strains than 3D7. Protein accession numbers, originating strain, domain structure and the closest related 3D7 var 5' sequence are shown along with sequence group allocations as defined in 3D7. *) The genes were assigned to group A, as their DBL1α sequences clustered together with other group A sequences in analysis of DBLα sequences. **) Pseudogene, belongs to the var1 family ^) Upstream sequences with atypically low similarity to upsB or upsC sequences.

Mentions: 13 var genes had 5' regions belonging to this group. The 10 closest related sequences of upsC aligned until a stretch of TA repeats around -4 kb from the translation initiation codon. The remaining three upsC sequences showed high upsC sequence similarity through the first 400 bp, but relatively low similarity over short stretches upstream. These were marked upsC^ in figure 7.


Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions.

Lavstsen T, Salanti A, Jensen AT, Arnot DE, Theander TG - Malar. J. (2003)

A) Schematic presentation of all 3D7 var gene sequence analyses. Gene names, chromosomal location, transcriptional direction and domain structure are shown along with the cluster to which each gene was assigned by the sequences analyses. Sequences that could not be assigned to any cluster were named X. Three major var gene groups (group A-C), two intermediate groups group B/A and group B/C and two unique genes representing var1 and var2 var gene families were defined (framed). B) Sequence analyses of var genes from other P. falciparum strains than 3D7. Protein accession numbers, originating strain, domain structure and the closest related 3D7 var 5' sequence are shown along with sequence group allocations as defined in 3D7. *) The genes were assigned to group A, as their DBL1α sequences clustered together with other group A sequences in analysis of DBLα sequences. **) Pseudogene, belongs to the var1 family ^) Upstream sequences with atypically low similarity to upsB or upsC sequences.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC222925&req=5

Figure 7: A) Schematic presentation of all 3D7 var gene sequence analyses. Gene names, chromosomal location, transcriptional direction and domain structure are shown along with the cluster to which each gene was assigned by the sequences analyses. Sequences that could not be assigned to any cluster were named X. Three major var gene groups (group A-C), two intermediate groups group B/A and group B/C and two unique genes representing var1 and var2 var gene families were defined (framed). B) Sequence analyses of var genes from other P. falciparum strains than 3D7. Protein accession numbers, originating strain, domain structure and the closest related 3D7 var 5' sequence are shown along with sequence group allocations as defined in 3D7. *) The genes were assigned to group A, as their DBL1α sequences clustered together with other group A sequences in analysis of DBLα sequences. **) Pseudogene, belongs to the var1 family ^) Upstream sequences with atypically low similarity to upsB or upsC sequences.
Mentions: 13 var genes had 5' regions belonging to this group. The 10 closest related sequences of upsC aligned until a stretch of TA repeats around -4 kb from the translation initiation codon. The remaining three upsC sequences showed high upsC sequence similarity through the first 400 bp, but relatively low similarity over short stretches upstream. These were marked upsC^ in figure 7.

Bottom Line: Two sequences belonging to the var1 and var2 subfamilies formed independent groups.A rif subgroup transcribed towards the centromere was found neighbouring var genes of group A such that the rif and var 5' regions merged.This organization appeared to be unique for the group A var genes The grouping of var genes implies that var gene recombination preferentially occurs within var gene groups and it is speculated that the groups reflect a functional diversification evolved to cope with the varying conditions of transmission and host immune response met by the parasite.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Medical Parasitology at Institute for Medical Microbiology and Immunology, University of Copenhagen, Denmark. thomaslavstsen@vip.cybercity.dk

ABSTRACT

Background: The variant surface antigen family Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) is an important target for protective immunity and is implicated in the pathology of malaria through its ability to adhere to host endothelial receptors. The sequence diversity and organization of the 3D7 PfEMP1 repertoire was investigated on the basis of the complete genome sequence.

Methods: Using two tree-building methods we analysed the coding and non-coding sequences of 3D7 var and rif genes as well as var genes of other parasite strains.

Results: var genes can be sub-grouped into three major groups (group A, B and C) and two intermediate groups B/A and B/C representing transitions between the three major groups. The best defined var group, group A, comprises telomeric genes transcribed towards the telomere encoding PfEMP1s with complex domain structures different from the 4-domain type dominant of groups B and C. Two sequences belonging to the var1 and var2 subfamilies formed independent groups. A rif subgroup transcribed towards the centromere was found neighbouring var genes of group A such that the rif and var 5' regions merged. This organization appeared to be unique for the group A var genes

Conclusion: The grouping of var genes implies that var gene recombination preferentially occurs within var gene groups and it is speculated that the groups reflect a functional diversification evolved to cope with the varying conditions of transmission and host immune response met by the parasite.

Show MeSH
Related in: MedlinePlus